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Introduction <p>Hypertrophic cardiomyopathy is an inherited cardiovascular disease with heterogeneous presentation. However, the metabolic changes resulting from mutations and their relationship to the phenotype remain unclear.</p> Objectives <p>To investigate the association between <i>TNNI3</i> and <i>MYBPC3</i> variants and both clinical phenotype and metabolic disorders in HCM patients.</p> Methods <p>34 newly diagnosed HCM patients, 51 healthy individuals, and 23 unaffected family members were included. Clinical information and plasma samples were collected and analyzed. Whole-exome and Sanger sequencing were used for variant identification. Non-targeted metabolomics was performed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry.</p> Results <p><i>TNNI3</i> and <i>MYBPC3</i> variants were identified in familial HCM cases, which exhibited earlier onset and increased interventricular septum thickness. Metabolomics revealed lower L-valine and higher free fatty acid levels in HCM patients. Patients with <i>TNNI3</i> variants showed dysregulation of lyso-phosphatidylcholines and lyso-phosphatidylethanolamines, along with disturbances in glutamic acid-related pathways. <i>MYBPC3</i> variants were linked to dysregulation in energy metabolism. Correlation analysis highlighted associations between specific lipid metabolites and cardiac structure and function.</p> Conclusion <p>Significant metabolic alterations, particularly in amino acid and lipid metabolism, are prevalent in HCM. These findings enhance our understanding of HCM pathogenesis and suggest potential biomarkers and therapeutic targets for this genetic heart disease.</p> Graphical Abstract <p></p>

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Association of TNNI3 and MYBPC3 variants with clinical phenotype and metabolic disorders in patients with hypertrophic cardiomyopathy

  • 期刊论文

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  • 发表日期：

    2026年7月11日

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  • Hao Wu,
  • Qiuyue Yu,
  • Huimin Li,
  • Zhulin Yang,
  • Hongjiang Zhang,
  • Dabing Ren,
  • Xiaoxue Ding,
  • Hong Zhang,
  • Yan Zhao,
  • Wenhua Su,
  • Lunzhao Yi

摘要

Introduction

Hypertrophic cardiomyopathy is an inherited cardiovascular disease with heterogeneous presentation. However, the metabolic changes resulting from mutations and their relationship to the phenotype remain unclear.

Objectives

To investigate the association between TNNI3 and MYBPC3 variants and both clinical phenotype and metabolic disorders in HCM patients.

Methods

34 newly diagnosed HCM patients, 51 healthy individuals, and 23 unaffected family members were included. Clinical information and plasma samples were collected and analyzed. Whole-exome and Sanger sequencing were used for variant identification. Non-targeted metabolomics was performed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry.

Results

TNNI3 and MYBPC3 variants were identified in familial HCM cases, which exhibited earlier onset and increased interventricular septum thickness. Metabolomics revealed lower L-valine and higher free fatty acid levels in HCM patients. Patients with TNNI3 variants showed dysregulation of lyso-phosphatidylcholines and lyso-phosphatidylethanolamines, along with disturbances in glutamic acid-related pathways. MYBPC3 variants were linked to dysregulation in energy metabolism. Correlation analysis highlighted associations between specific lipid metabolites and cardiac structure and function.

Conclusion

Significant metabolic alterations, particularly in amino acid and lipid metabolism, are prevalent in HCM. These findings enhance our understanding of HCM pathogenesis and suggest potential biomarkers and therapeutic targets for this genetic heart disease.

Graphical Abstract